Epigenetics in human gliomas
Cancer LettersPublished 21 April 2012
Simone Kreth, Niklas Thon, Friedrich W. Kreth
Citations67
SJR quartileQ1
SJR score2.76
SNIP1.54
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TL;DR
The basic principles of epigenetic control in gliomas are addressed, their current and putative future role in prognostic and predictive models and possible interactions within the epigenetic network are presented, and diagnostic and therapeutic opportunities appearing at horizon of epigenetics research are discussed.
Abstract
Aberrant epigenetic landscapes and their involvement in genesis and progression of tumors, as well as in treatment responses and prognosis, indicate one of the most emerging fields in cancer research. In gliomas, the most common human primary brain tumors, and in particular in glioblastoma, the most malignant and devastating brain tumor entity in adults, the elucidation of distinct patterns of aberrant DNA methylation, histone modification, and miRNA expression and their interrelationship has fundamentally changed our point of view on these highly heterogeneous tumors. In the current review article, we address the basic principles of epigenetic control in gliomas, their current and putative future role in prognostic and predictive models and possible interactions within the epigenetic network. We discuss diagnostic and therapeutic opportunities appearing at horizon of epigenetic research. Moreover, we present current and propose future clinical workflow models for molecular characterization of malignant gliomas.
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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Cancer ResearchGenome-wide Hypomethylation in Human Glioblastomas Associated with Specific Copy Number Alteration, Methylenetetrahydrofolate Reductase Allele Status, and Increased Proliferation
231 Citations2006Benoît Cadieux, Tsui‐Ting Ching +2 more
It is reported that global hypomethylation is common in primary human glioblastomas [glioblastoma multiforme (GBM] and can affect up to an estimated 10 million CpG dinucleotides per haploid tumor genome, and that MTHFR deficiency-associated demethylation leads to increased proliferative activity in GBM.
Cell CycleCpG Island Hypermethylation of Tumor Suppressor microRNAs in Human Cancer
210 Citations2007Amaia Lujambio
In the coming years, the relevance of this expected encounter between two forces – epigenetics and microRNAs – that are currently at the forefront of biology will come to realize more fully.
PLoS ONEGenetic and Epigenetic Modifications of Sox2 Contribute to the Invasive Phenotype of Malignant Gliomas
209 Citations2011Marta M. Alonso, Ricardo Díez-Valle +18 more
E ectopic Sox2 expression was sufficient to induce invasion and migration of glioma cells, and knockdown experiments demonstrated that Sox2 was essential for maintaining these properties, which underscore the importance of a pleiotropic role of Sox2 and suggest that it could be used as a therapeutic target in GBM.
Proceedings of the National Academy of SciencesEpigenetic inactivation of the Sotos overgrowth syndrome gene histone methyltransferase NSD1 in human neuroblastoma and glioma
207 Citations2009María Berdasco, Santiago Ropero +8 more
It is reported that NSD1 function is abrogated in human neuroblastoma and glioma cells by transcriptional silencing associated with CpG island-promoter hypermethylation and it is demonstrated that the epigenetic inactivation of N SD1 in transformed cells leads to the specifically diminished methylation of the histone lysine residues H4-K20 and H3-K36.
Medical intelligence unitCpG Island Hypermethylation of Tumor Suppressor Genes in Human Cancer
203 Citations2007Michel Herranz, Manel Esteller
In the coming years, the relevance of this expected encounter between two forces-epigenetics and microRNAs-that are currently at the forefront of biology will come to realize more fully the relevance.
Neuro-OncologyIdentification of microRNAs in the cerebrospinal fluid as biomarker for the diagnosis of glioma
197 Citations2011Alexander Baraniskin, Jan Kuhnhenn +6 more
MiR-15b and miR-21 are markers for gliomas, which can be assessed in the CSF by means of qRT-PCR, and have the potential to serve as novel biomarkers for the detection of glioma.
Journal of NeurochemistryA specific miRNA signature in the peripheral blood of glioblastoma patients
197 Citations2011Patrick Roth, Jörg Wischhusen +6 more
OncogenePro-neural miR-128 is a glioma tumor suppressor that targets mitogenic kinases
185 Citations2011Thales Papagiannakopoulos, Dinorah Friedmann‐Morvinski +10 more
Pro-neuronal miR-128 is identified as a glioma tumor suppressor that targets RTK signaling to repress giNSC self-renewal and enhance differentiation and repressed gliomagenesis.
EpigeneticsA microarray-based DNA methylation study of glioblastoma multiforme
172 Citations2009Ramón Martínez, José I. Martín‐Subero +7 more
The DNA methylation level of 1,505 CpG dinucleotides (807 genes) in 87 consecutive GBMs using universal BeadArrays is quantified and the group of genes hypermethylated in GBM was highly enriched (41%, P).
OncogenemiR-221/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTPμ
171 Citations2011Cristina Quintavalle, Michela Garofalo +9 more
The results suggest that miR-221 and -222 regulate glioma tumorigenesis at least in part through the control of PTPμ protein expression.
Molecular and Cellular BiologyMicroRNA-146a Inhibits Glioma Development by Targeting Notch1
171 Citations2011Jie Mei, Robert Bachoo +1 more
Findings indicate that miR-146a is induced as a negative-feedback mechanism to restrict tumor growth by repressing Notch1, which provides novel insights into the signaling pathways that link neural stem cells to gliomagenesis and may lead to new strategies for treating brain tumors.
Clinical Cancer ResearchSuberoylanilide Hydroxamic Acid, a Histone Deacetylase Inhibitor: Effects on Gene Expression and Growth of Glioma Cells <i>In vitro</i> and <i>In vivo</i>
169 Citations2007Dong Yin, John M. Ong +6 more
Taken together, SAHA can slow the growth of GBM in vitro and intracranially in vivo and may be a welcome addition for the treatment of this devastating disease.
Brain Tumor PathologyGenetic profile of astrocytic and oligodendroglial gliomas
163 Citations2011Hiroko Ohgaki, Paul Kleihues
The high frequency of IDH1/2 mutations in oligodendrogliomas, astrocytomas, and secondary glioblastomas derived thereof suggests these tumors share a common progenitor cell population.
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